期刊
SCIENCE
卷 369, 期 6511, 页码 1603-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abc4730
关键词
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资金
- National Key Plan for Scientific Research and Development of China [2016YFD0500304, 2016YFD0500306, 2020YFA0707801]
- National Natural Science Foundation of China [82041006, 82041025]
- National Science and Technology Major Project of China [2018ZX09711003, 2017ZX10304402003]
- Beijing Municipal Science and Technology Project [Z201100001020004]
- National Science Fund for Distinguished Young Scholar [81925025]
- Innovative Research Group from the NSFC [81621005]
- CAMS Innovation Fund for Medical Sciences [2019-I2M-5-049]
The ongoing coronavirus disease 2019 (COVID-19) pandemic has prioritized the development of small-animal models for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We adapted a clinical isolate of SARS-CoV-2 by serial passaging in the respiratory tract of aged BALB/c mice. The resulting mouse-adapted strain at passage 6 (called MASCp6) showed increased infectivity in mouse lung and led to interstitial pneumonia and inflammatory responses in both young and aged mice after intranasal inoculation. Deep sequencing revealed a panel of adaptive mutations potentially associated with the increased virulence. In particular, the N501Y mutation is located at the receptor binding domain (RBD) of the spike protein. The protective efficacy of a recombinant RBD vaccine candidate was validated by using this model. Thus, this mouse-adapted strain and associated challenge model should be of value in evaluating vaccines and antivirals against SARS-CoV-2.
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